Imagine if there were an organ in your body that weighed as much as your brain, that affected your health, your weight, and even your behavior. Wouldn’t you want to know more about it? There is such an organ — the collection of microbes in and on your body, your human microbiome.

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BF

Both enjoyable and challenging. Hear an interesting range of lectures, backed up with a wide range of articles. Shook up my idea of what it takes to be a healthy human - a healthy microbiome.

MH

May 09, 2020

Filled StarFilled StarFilled StarFilled StarFilled Star

One of the best courses I've ever taken online. The food log assignments - reflections & final project are immensely beneficial. If you're curious about your microbes, don't miss this course.

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Introduction to Microbes and the Human Microbiome

Welcome Citizen Scientists! We're very pleased to have you join us on an exploration of the human microbiome. This is a fascinating area of study, and we hope you will find this six-module course worthwhile. Each module's content will be presented in similar fashion; our team will introduce topics by way of pre-recorded video lectures interspersed with guest interviews by subject matter experts. Module 1 will provide a broad overview about microbes and their diversity on earth and in the human body.

Преподаватели

Rob Knight

Dr. Jessica L. Metcalf

Dr. Katherine R. Amato

Текст видео

We humans have always been really concerned about the health of our bodies. But, we haven't always been that good at figuring out what parts are important. Take the ancient Egyptians, for example. They were very careful to preserve the parts of their bodies that they knew they would need in the afterlife. The heart, the liver, the intestines and so forth. But there were other parts of the body that they were somewhat less careful with. The brain for example, which essentially they just mushed up with metal or wooden tools, drained out through the nose, and threw away. Which makes sense in a way really, because what has the brain ever done for us anyway? Imagine if you have a, had an organ which had been overworked, that weighed about as much as the brain, and in some ways was just as important to who we are. But that we knew even less about, and that we treated with such disregard. Wouldn't you want to know more about it, especially if it was turning out that new technologies and new techniques were letting us dis, make discoveries about it at an unprecedented rate? Well it turns out that we do have something just like that. Our gut microbes, and indeed the microbes all over the rest of our body. So a clutch of microbes weighs about three pounds, about as much as a brain, and in some ways that turns out to be incredibly important for determining all kinds of important things about who we are. For example, the microbes that you have in your gut determine whether or not some medications are toxic to your liver. For example, the drug Acetaminophen, which is the active ingredient in Tylenol, or Paracetamol, for those of you watching us internationally. Whether or not that's toxic to your liver, it depends in great part on whether or not you have particular groups of sulfite reducing microbes near your gut. Similarly, the microbes that we have help us digest our food, and in some cases they seem to eat and steal genes from our food in order to help us digest it. Fascinatingly, it turns out that a Japanese population that was studied where of course, sushi is relished with prevalently, are prevalently eaten. Their gut bacteria have some genes that previously had only been found in a group of marine bacteria that feed exclusively on seaweed. And apparently those those seaweed eating bacteria had transferred some of their genes to the genes in the gut of this Japanese population. And when, when the researchers who did this paper compared the Japanese population to a population that we study with Jeffrey Golden's lab in St. Louis. The, the population in St. Louis didn't have any of those same genes for dig, for degrading seaweed at all. I guess the only thing I'll say about that, is that if you haven't tried this issue in St. Louis, I really wouldn't recommend it. So, you can see how seaweed consumption might be a lot, a lot lower there. So the microbes that you have in your gut may even depend on whether, whether your diet works. So a group of French researchers associated with the Matterhead project, now lead by performed a really elegant study where what they did is they put a group of people on a, on a diet. They asked could they predict who the diet would work for based on the, based on the microbes that they had before they started the diet. And fascinatingly, how much weight they lost depended substantially on what microbes they had in their gut before. So there's a whole range of reasons that you should care about your microbes beyond the ones that they discussed. Some of the, some of their other functions are that they train your immune system. And they may influence be, your behavior and affect your health in all kinds of subtle ways. Or even obvious ways that we're only just now beginning to discover. So let's throw out a few numbers about our microbes. What would, what we're starting to discover about the microbiome, may even lead us to reconsider how human we are in the first place. So, for example, each of us consists of about 10 trillion human cells, but we have as many as 100 trillion microbial cells on and inside our bodies. So in any case they outnumber us by about ten, ten to one in terms of the sheer count of cells. And by this count we're only about 10% human. But you might say, hey wait a minute, it's really our DNA that makes us human, our genes. So let's think about this in terms of our genes. Each of us has about 20,000 human genes depending on what exactly what exactly we count. But we have between two and 20 million microbial genes. And so by the count of the unique genes that we have associated with us, we're really only 1% to 0.1% human. So this is really remarkable in a way, right? The three pounds of microbes that we carry around with us has ten, ten times as many cells, and 100 to 1000 times as many genes as our own bodies and our own genomes. Now let's think about this in terms of similarity. As you probably heard from the results of the human genome project, and especially the human genome diversity project, each of us shares essentially all of our DNA, so so, let's say for example you and the person you're sitting next to will share 99.99% of your DNA, on average. But then, when you consider how much of your microbiome you share, probably you're 90% different in terms of your microbiome. So, in other words, what this means is that you are perhaps not a beautiful and unique snowflake genetically, but but perhaps your particular collection of microbial symbiance is. So let's get into a few definitions, because there's a lot of confusion about the microbiome versus the microbiota. When we're talking about the human microbiota, what we're talking about is a particular community of microbes that inhabits a particular location in the human body. And strictly this will contain everything, including the bacteria, the archaea, the viruses and very tiny eukaryotes. Which are cells that, like our own human cells, contain nuclei. But in this case, they're typically single cell single celled organisms. Where that one cell lives free by itself rather than making up a more complex organism. However, in many of the studies of the human microbiota because of technical limitations we're going to be focused on the bacteria. Which although they can probably surpass the majority of the microbiota, some of those other components, especially the viruses and the eukaryotes can be important as well. Now this is in contrast to the human microbiome. So the human microbiome is the collection of all of the genes that are contained in the microbiota. And so as I said when we're talking about the microbiome, strictly, we're talking about the gene level, as opposed to the microbiota, where we're talking about the organism level. So with respect to the microbiota, you might be wondering, is everything everywhere, do the same organisms exist everywhere on the planet, and everywhere inside our own bodies? In particular you might expect that, for example, because your mouth is connected to your gut, via your stomach and so on, because of that continuity, you might expect more or less the same microbes with some variation, to show up all the way through your gastrointestinal tract. But it turns out that the body is really an ecosystem that has as many distinct habitats. They can be very different from one another. So, one way to think about it is just in, just as in the same way different parts of the world have these different landscapes with different characteristic animals that allow you to immediately identify scenes coming, let's say, from the Arctic or from Africa or from Australia. In the same way there are particular, there are particular organisms that very characteristically live in one part of the body. But not anywhere else. We can think of a map of our own body in the same way that we think of a map of, of our world, where there's characteristic bio-geography, that distinguishes different places. So, with this in mind, let's go on a tour of the human ecosystem. Let's start this tour with our skin. So, so the skin is the body's largest organ, and in addition to providing barrier, begins the outside world. It also produces different kinds of, dif, different kinds of compounds that smell. Sometimes attractive sell, smells, sometimes unattractive smells. And, these are things that, these, these are things that we use for signaling to each other. For example, how attractive you find someone, depends somewhat on the volatile compounds that are coming up the skin. Another reason why it's important they always said that it determines their attractiveness to mosquitos. So, for example it turns out that everyone's anecdotal experience of camping is actually true. Some people really do get bitten vastly more frequently by mosquitos than others. As an example my partner, my partner Amanda attracts mosquitos in droves. Whereas I relatively seldom get bitten, and so as a result, this has in, in the past lead to a lot of disagreements when, when we go camping together. Right, but it turns out that your experience of camping like that is literally true. You might be ten times as attractive to mosquitos as the person you're going camping with. One, one thing that's interesting is that the skin microbiome is extremely heterogeneous. It's very different in different parts of the body. For example, the armpits and the foreheads have very high densities of microbes, but relatively few different types of microbes in each of loca, each of those locations. Whereas in contrast, the palm of your hand have a lot of different types, but relatively few total microbial cells. But the skin communities all, also do have their own characteristic organisms. So for example, Propionibacterium acnes, which was the bacterium that can cause acne in some people, although in many other people it's completely harmless, is one of the dominant constituents of the skin. And it can make up 80% of the, of the microbes on the palm of your hand. Another really common skin microbe is Staphylococcus epidermiditis, which is a harmless relative of the potentially dangerous Staph aureus which you might have heard of. And so and so some of the other genera that are common on the skin are Corynebacterium streptococcus and various kinds of proteobacteria. I'll just talk briefly about the bacteria in the respiratory tract. The nose has a relatively distinct micro, microbiome. And one hallmark of this microbiome is Staphylococcus aureus, which is often thought of as a pathogen, although again many of the people who have it, it don't have any symptoms or any infections. And so what we think is going on inside of the nose might be controlled by other bacteria, that are generally innocuous. Then, additionally by the antimicrobial peptides that we produce. One thing that's fascinating though is that children who have a higher diversity, in other words, more different kinds of bacteria in their noses. Grow up to have fewer allergies and lower incidents of asthma than children who have less diverse microbial communities. One interesting point is the lungs. So we used to think that healthy lungs only had dead bacteria, but in people with chronic lung diseases such as cystic fibrosis COPD and so forth. What we see is actual living populations of microbes in the lungs. And those microbes in some cases are contributing to those diseases such as the biotomes of Pseudomonas which are a leading cause of death for cystic fibrosis patients. Next we're going to move onto the math, which and, and we often think of we often only think of the oral microbes that cause tooth decay and gingivitis, like Streptococcus mutans for example. And every time you go to the dentist, you're probably going to get a long explanation about how you need to floss to keep down the bad bacteria. In contrast, though, most of the bacteria in the, in the mouth are beneficial and in fact, they can lay down path, they, they can lay down biofilms that actually prevent the pathogens from getting a good foothold. So most people, in the mouth the Streptococcus species are merely different kinds of the most abundant microbes although this, although this range of other things in there. Like fuschia bacterium nucleatum, for example, which we'll also hear about later in the context of cancer. Well it turns out the microbes of the mouth differ greatly depending on what part of the mouth you're looking at. The mouth has a fascinating biogeography all of its own. And even the same teeth can have different bacteria on one side versus the other. So next we go to move down the GI tract and move into the gut. So so the gut is really the center of microbial activity in the human body with most of those estimated 100 trillion bacterial cells that we've been talking about. And so the gut, and so the gut microbes have been studied a lot more than the microbes in the other parts of the body, other parts of the body for two reasons. The first of these reasons is that its the largest, most important community and in addition to that it's really easy to sample because everyone poops, right? However people mostly sample at the far end of the large intestine it does represent a pretty good a pretty good average of the microbes in that, in that distal part of your gut. However what, what you should be aware of is the microbes in your small intestine are very different from the microbes in your large intestine. And those differences can be much tougher, much greater than the differences between different people. However what's kind of interesting is that the the, the, the gut mucosa, so, the lining of your gut tends to have a bacterial community. But although somewhat shifted from the, from the community in the poop, there's often less different than, than the difference between different people. And so you can use some of the poop as a pretty good read-out of what's going on inside each individual person. Now that's not true just for different people. The poop also provides a really good representation of the difference between different animals. And as we'll see later on, this turns out to be really important when you want to go to the zoo and compare a whole lot of different animals in terms of what kinds of microbes they have associated with them. Because annoying as it is to do a colonoscopy on a person, it's much, much worse if you need to do that on a giraffe or on a rhino, especially if the rhino is not really that into having the colonoscopy. So we most commonly sample the gut using these fecal samples because they are noninvasive and because they are so easy to obtain. Now we traditionally think of E coli as an important gut microbe. But the reason we think of it that way isn't that it's a dominant player in the gut community, rather it's just that it's really really good at growing on the petri dish. So it provides a nice lab rat, but it's very unlike the vast majority of the microbes that, that we can't, that we can't keep in the equivalent of the zoo. So, we know a lot about E coli, but it's not really that important to get microbial ecology in most healthy people, and typically it's less than one cell in a million in healthy adults. So, what's really in the gut? Well, the two main groups we have in there are the phomocutes and the bacterodetis, which help to digest food, metabolize drugs and all kinds of other, all kinds of other important functions. And we're still learning about them and their possible ro, roles in health and disease, as we'll find out through the rest of the course. So, in conclusion, the human body really is an ecosystem, each of us carries around an incredible diversity of kinds of microbes, living right there inside our bodies. Disregarding the microbiota and disregarding the microbiome is, potentially is foolish, is throwing away the brain as a useless organ. And what's really amazing is that as a poop, which many of us think is the epitome of something we produce that has no value, and that that we just flush down the toilet everyday. May in fact be incredibly valuable and hold the keys to finding out what's going on there right inside our own bodies.